A high dietary acid load can potentially exacerbate cardiometabolic risk factors: An updated systematic review and meta-analysis of observational studies.

AIMS: Chronic metabolic acidosis has been shown to be associated with cardiometabolic risk factors. The aim of the currently updated meta-analysis was to explore the association between Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) with these risk factors. DATA SYNTHESIS: Databases were searched up to May 2023. The mean of waist circumference (WC), body mass index (BMI), high- and low-density lipoprotein-cholesterol (HDL-C and LDL-C), triglyceride (TG), total cholesterol (TC), fasting blood sugar (FBS), and systolic- and diastolic blood pressure (SBP and DBP) in highest category vs lowest categories of NEAP and PRAL were recorded. Effect sizes were generated as weighted mean difference (WMD). Results showed that SBP, DBP, and WC had a significant difference in the upper and lower categories of PRAL (WMDSBP: 1.466 mmHg; 95% CI: 2.121, -0.811; P<0.001, WMDDBP: 0.710 mmHg; 95 % CI: 1.170, -0.249; P=0.003, and WMDWC: 0.819 cm; 95% CI: 1.446, -0.192; P=0.010) or NEAP (WMDSBP: 1.690 mmHg; 95% CI: 2.789, -0.591; P=0.003, WMDDBP: 1.076 mmHg, and WMDWC: 1.325 cm; 95% CI: 1.901, -0.749; P<0.001; 95% CI: 1.938, -0.214; P =0.014). The lowest versus highest categories of dietary PRAL were associated with lower BMI (WMDPRAL: 0.297 kg/m2; 95 % CI: 0.440, -0.154; P<0.001) and TG (WMD: 2.280 mg/dl; 95%CI: 3.828, -0.732; P=0.004; I2=99.4 %; P<0.001). CONCLUSIONS: High DAL can be considered as an independent risk factor for increasing anthropometric indices, blood pressure, and TG. This study registered in the PROSPERO database (Registration No. CRD42023402985).

The Interplay of Comorbidities in Chronic Heart Failure: Challenges and Solutions.

BACKGROUND: Chronic heart failure (HF) is frequently associated with various comorbidities. These comorbid conditions, such as anemia, diabetes mellitus, renal insufficiency, and sleep apnea, can significantly impact the prognosis of patients with HF. OBJECTIVE: This review aims to synthesize current evidence on the prevalence, impact, and management of comorbidities in patients with chronic HF. METHODS: A comprehensive review was conducted, with a rigorous selection process. Out of an initial pool of 59,030 articles identified across various research modalities, 134 articles were chosen for inclusion. The selection spanned various research methods, from randomized controlled trials to observational studies. RESULTS: Comorbidities are highly prevalent in patients with HF and contribute to increased hospitalization rates and mortality. Despite advances in therapies for HF with reduced ejection fraction, options for treating HF with preserved ejection fraction remain sparse. Existing treatment protocols often lack standardization, reflecting a limited understanding of the intricate relationships between HF and associated comorbidities. CONCLUSION: There is a pressing need for a multidisciplinary, tailored approach to manage HF and its intricate comorbidities. This review underscores the importance of ongoing research efforts to devise targeted treatment strategies for HF patients with various comorbid conditions.

Polypharmacy, Gender Disparities, and Ethnic and Racial Predispositions in Long QT Syndrome: An In-Depth Review.

Long QT syndrome (LQTS) is a complex disorder of cardiac electrophysiology. It is characterized by delayed myocardial polarization leading to QT prolongation and alterations on the ST segment and T wave visible on electrocardiogram (ECG). Syncope is a common manifestation, and torsade de pointes (TdP) can lead to sudden cardiac death. Three major LQTS genes (KCI31, KCNH2, and SCN5) lead to most of the cases of LQTS. Lifestyle modifications, beta blockers, and implantable cardioverter defibrillator (ICD) placement are the main treatments for LQTS. Polypharmacy, including QT-prolonging drugs, has been shown to worsen LQTS. The impact on potassium channels and the human ether-a-go-go-related gene (hERG) is the mechanism behind the QT interval prolongation caused by these medications. There is an increased incidence of LQTS among African-American men and women as compared to Caucasians. Women with LQTS tend to have a higher mortality rate from the condition, especially during menstruation and shortly after giving birth. Genetic testing is reserved to those patientswho exhibit either a strong clinical index of suspicion or experience persistent QT prolongation despite their lack of symptoms. Knowing the genetics, racial, and gender discrepancies can help improve patient management and a better comprehension on each case. Proper understanding of how ion channels function and their interaction with medications will lead to a better comprehension and to develop effective forms to treat those patients.

Alleviating effects of coenzyme Q10 supplements on biomarkers of inflammation and oxidative stress: results from an umbrella meta-analysis.

Introduction: Although several meta-analyses support the positive effect of coenzyme Q10 (CoQ10) on biomarkers of oxidative stress and inflammation, the results of some other studies reject such effects. Methods: Therefore, in this umbrella meta-analysis, we performed a comprehensive systematic search in such databases as Web of Science, PubMed, Scopus, Embase, and Google Scholar up to January 2023. Results: Based on standardized mean difference analysis, CoQ10 supplementation significantly decreased serum C-reactive protein (CRP) (ESSMD = -0.39; 95% CI: 0.77, -0.01, p = 0.042) and malondialdehyde (MDA) (ESSMD = -1.17; 95% CI: 1.55, -0.79, p < 0.001), while it increased the total antioxidant capacity (TAC) (ESSMD = 1.21; 95% CI: 0.61, 1.81, p < 0.001) and serum superoxide dismutase (SOD) activity (ESSMD = 1.08; 95% CI: 0.37, 1.79, p = 0.003). However, CoQ10 supplementation had no significant reducing effect on tumor-necrosis factor-alpha (TNF- α) (ESSMD = -0.70; 95% CI: 2.09, 0.68, p = 0.320) and interleukin-6 (IL-6) levels (ESSMD = -0.85; 95% CI: 1.71, 0.01, p = 0.053). Based on weighted mean difference analysis, CoQ10 supplementation considerably decreased TNF-α (ESWMD = -0.46, 95% CI: 0.65, -0.27; p < 0.001), IL-6 (ESWMD = -0.92, 95% CI: 1.40, -0.45; p < 0.001), and CRP levels (effect sizes WMD = -0.28, 95% CI: 0.47, -0.09; p < 0.001). Discussion: The results of our meta-analysis supported the alleviating effects of CoQ10 on markers of inflammation cautiously. However, CoQ10 had antioxidant effects regarding the improvement of all the studied antioxidant and oxidative stress biomarkers. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=323861, identifier CRD42022323861.

Cigarette smoking trajectories among adolescents and young adults in the Islamic Republic of Iran.

Background: Cigarette smoking follows a progressive pattern throughout the lifetime; most adult smokers started smoking during adolescence. Aim: To understand the cigarette smoking trajectories and their predictors among adolescents and young adults in the Islamic Republic of Iran. Methods: Using data from the Tehran Lipid and Glucose Study, we followed 1169 adolescents (12-18 years old) into their young adulthood (28-32 years old), from 2002 to 2016. We used cigarette smoking as the outcome variable for group-based trajectory modelling. After detecting the trajectories, we investigated the effects of independent variables, namely, individual employment; education; physical activity; and paternal smoking, employment and education, on the trajectories. We analysed the data using STATA version 16 and SPSS version 26. Results: Three trajectories were detected: non-smokers (79%), experimenters (12%) and escalators (9%). Boys were approximately 3 times (OR = 2.94, 95% CI: 2.32-3.24, P < 0.001) and 25 times (OR = 25.00, 95% CI: 23.92-26.08, P < 0.001), respectively, more likely than girls to be in the experimenter and escalator groups. Receiving a university education decreased the odds of being in the escalator trajectory for 18% (OR = 0.82, 95% CI: -0.04-0.96, P = 0.002) of the study participants. Employment after high school increased the odds by approximately two folds for the experimenter (OR = 2.00, 95% CI: 1.42-2.50, P = 0.01) and escalator (OR = 2.33, 95% CI: 1.33-2.93, P = 0.03) trajectories. Paternal smoking was associated with 1.88 and 2.23, respectively, increased odds of experimenting and escalating smoking among the adolescents. Conclusion: Iranian adolescents follow 3 cigarette smoking trajectories into young adulthood: non-smokers, experimenters and escalators. Male sex, employment after high school, and living with a smoker father were associated with unfavourable smoking patterns. Findings from this study provide valuable insights for designing targeted interventions to reduce cigarette smoking among adults and adolescents in the Islamic Republic of Iran.

Effectiveness of a practical multi-setting lifestyle intervention on the main BMI trajectories from childhood to young adulthood: A community-based trial.

BACKGROUND: Preventing overweight in childhood and subsequent stages of life is still a global challenge. Despite numerous relevant lifestyle interventions, data on their impact on different BMI change pathways over time is rare. The present study aimed to investigate the effect of a multi-setting lifestyle intervention on BMI trajectories from childhood to young adulthood. METHODS: A multi-setting lifestyle intervention at the school, family, and community levels have been conducted in the Tehran Lipid and Glucose Study framework. A total of 2145 children (4-18 years, 49% boys, and 18% intervention) were recruited for the baseline assessment and were followed through five follow-up examinations during a median of 16.1 years. Using a group-based trajectory model, BMI trajectories from childhood to young adulthood were identified, and their association with the implemented intervention was assessed. RESULTS: Four trajectory groups of BMI from childhood to young adulthood were identified, including Normal weight (41%), Young adulthood overweight (36%), Early childhood increasing overweight and adulthood obesity (19%), and Early childhood increasing obesity (4%). Only Young adulthood overweight and Early childhood increasing obesity were affected by the intervention and were concomitant with lower BMI levels than the control group, with the highest estimated effect in the latter (ß=-0.52 and p = 0.018; ß=-1.48 and p < 0.001, respectively). CONCLUSION: The current findings indicate the highest effectiveness of a practical, healthy lifestyle intervention on those whose obesity started in the early years of life or youth. Our results could help policymakers and planners design more targeted lifestyle modification and weight control interventions. TRIAL REGISTRATION: This study is registered at Iran Registry for Clinical Trials, a WHO primary registry ( http://irct.ir ). The Iran Registry for Clinical Trials ID and date are IRCTID:IRCT138705301058N1, 29/10/2008.

A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2.

Currently, the world is facing a pandemic of the new coronavirus SARS-CoV-2 that causes COVID-19. Identifying key targets in the viral infection lifecycle is urgently needed for designing therapeutic strategies to combat the virus. Furin is a subtilisin-like proprotein convertase with diverse cellular functions. Emerging evidence suggests that furin plays a critical role in the activation and/or infectivity of SARS-CoV-2. In this perspective, we discuss the potential role of furin in the entry SARS-CoV-2 into host cells. Furthermore, we evaluate available peptide and non-peptide furin inhibitors and potential outcomes, including immune responses.